POTENTIAL ROLE OF ENDOTHELIAL CELLS AND BMP7 IN VASCULOGENIC MIMICRY FORMATION IN CERVICAL CANCER

BIRKENSTOCK CINTIA; NOVOA DÍAZ BELEN; CARRIERE PEDRO MATÍAS; CALVO, NATALIA; HOMANN L; GENTILI, CLAUDIA

Mar del Plata

Congreso; LXVII Reunión Anual de Sociedades de Biociencias (SAIC); 2022

Sociedad Argentina de Investigación Clínica

Vasculogenic mimicry (VM) is an alternative microvascular system in which highly invasive tumor cells mimic endothelial cells by forming blood vessel-like structures. This process is correlated with poor prognosis, metastasis, and resistance to anti-angiogenic therapy in various cancers, including cervical cancer (CC). We previously observed that after treatment with conditioned media from CC-derived HeLa cells (TCMs) for 24 hours, HMEC-1 cells acquire characteristics related to endothelial cells found in the tumor microenvironment niche. In addition, we found that the signaling pathway of bone morphogenetic protein 7 (BMP7) could be involved. The objective of this work was to investigate whether endothelial cells with characteristics related to those found in the tumor microenvironment are involved in the formation of VM in CC and the potential role of BMP7 in this process. Initially, we evaluated whether the factors released by endothelial cells with characteristics related to those found in the tumor niche promote VM formation in CC. The HMEC-1 cells were treated for 24 hours with TCM from HeLa cells, followed by a medium renewal to obtain a new conditioned medium (ECM-T). Using qRT-PCR, we observed that exposure of HeLa cells with these ECM-T increase the mRNA levels of markers associated with VM, VE-cadherin, EphA2 and vimentin. The protein-protein interaction network by the STRING database identified interactions between BMP7 and 12 genes involved in MV formation. Furthermore, incubating HeLa cells with the ECM-T also promotes tube-like structure formation. These effects were partially reversed by pre-incubating TCM from HeLa cells with an antibody against BMP7. These results suggest a potential indirect role of BMP7 in the VM in CC by acting on endothelial cells. Expanding the knowledge of the molecular mechanisms associated with VM in CC will help identify potential biomarkers that predict the prognosis and resistance to anti-angiogenic therapy.